Abstract

Treatment of severe traumatic brain injury (TBI) in the intensive care unit focuses on controlling intracranial pressure, ensuring sufficient cerebral perfusion, and monitoring for secondary injuries. However, there are limited prognostic tools and no biomarkers or tests of the evolving neuropathology. Metabolomics has the potential to be a powerful tool to indirectly monitor evolving dysfunctional metabolism. We compared metabolite levels in simultaneously collected arterial and jugular venous samples in acute TBI patients undergoing intensive care as well as in healthy control volunteers. Our results show that, first, many circulating metabolites are decreased in TBI patients compared with healthy controls days after injury; both proline and hydroxyproline were depleted by ≥60% compared with healthy controls, as was gluconate. Second, both arterial and jugular venous plasma metabolomic analysis separates TBI patients from healthy controls and shows that distinct combinations of metabolites are driving the group separation in the two blood types. Third, TBI patients under heavy sedation with pentobarbital at the time of blood collection were discernibly different from patients not receiving pentobarbital. These results highlight the importance of accounting for medications in metabolomics analysis. Jugular venous plasma metabolomics shows potential as a minimally invasive tool to identify and study dysfunctional cerebral metabolism after TBI.

Keywords:
human; jugular venous blood; metabolomics; pentobarbital.

Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.
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Visualization of changes in metabolites…

FIG. 1.
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Visualization of changes in metabolites between groups by volcano plot in (A) arterial…

FIG. 1.

Visualization of changes in metabolites between groups by volcano plot in (A) arterial and (B) jugular venous blood. Volcano plots visualize the fold change between groups as a function of the significance level of the statistical test performed. Metabolites above the horizontal dashed line are considered to significantly change between groups (false discovery rate [FDR] adjusted p value <0.05). Vertical dotted lines indicate, from left to right, fold changes of 0.6, 0.75, 1.33, and 1.66.